ASSOCIATION BETWEEN POLYMORPHISM OF FOLATE AND METHIONINE METABOLISM RELATED GENES AND ABERRANT DNA METHYLATION IN PATIENTS WITH MYELODYSPLASTIC SYNDROME
(Abstract release date: 05/19/16)
EHA Library. Sidorova Z. 06/09/16; 134805; PB1905
Dr. Zhanna Sidorova
Contributions
Contributions
Abstract
Abstract: PB1905
Type: Publication Only
Background
Abnormal DNA methylation is often seen in patients with myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation process and, therefore, modify the risk of MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in MDS patients.
Methods
Fifty-one patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Twenty-one patients (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG) and 30 patients (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG).The MTRR 66 GG genotype was more frequently seen in the group 0-2 MG than in the group 3-5 MG (47.6% vs 13.3%, respectively, OR=5.9, 95%CI: 1.5-22.9, p=0.011). The MTHFR 1298 CC variant was present in 6 patients from the 3-5 MG and in 1 patient from the group 0-2 MG and (20.8% vs 4.8%, respectively, OR=5.0, 95%CI: 0.6-45.1, p=0.2).The presence of the MTHFR 677T allele was increased in male patients from the group 0-2 MG when compared to male patients in the 3-5 MG group (100% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01), and female patients from the 0-2 MG group (100% vs. 33.4%, respectively, OR=35.9, 95%CI: 1.7-770, p=0.005). At the same time, positivity for the MTHFR 677T allele was not different between women from 0-2 MG and 3-5 MG groups (33.4% vs. 46.7%, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7).The simultaneous presence of the MTHFR 677T allele and MTRR 66GG genotype was more often detected in the 0-2 MG group than in the 3-5 MG group (33.3% vs. 10.0%, OR=4.5, 95%CI: 1.0-20.1, p=0.07).
Conclusion
We conclude that polymorphism of the FMM related genes could have an important role in mechanism of epigenetic disturbances in MDS associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): Genetic polymorphism, MDS, Methylation
Type: Publication Only
Background
Abnormal DNA methylation is often seen in patients with myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation process and, therefore, modify the risk of MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in MDS patients.
Methods
Fifty-one patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Twenty-one patients (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG) and 30 patients (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG).The MTRR 66 GG genotype was more frequently seen in the group 0-2 MG than in the group 3-5 MG (47.6% vs 13.3%, respectively, OR=5.9, 95%CI: 1.5-22.9, p=0.011). The MTHFR 1298 CC variant was present in 6 patients from the 3-5 MG and in 1 patient from the group 0-2 MG and (20.8% vs 4.8%, respectively, OR=5.0, 95%CI: 0.6-45.1, p=0.2).The presence of the MTHFR 677T allele was increased in male patients from the group 0-2 MG when compared to male patients in the 3-5 MG group (100% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01), and female patients from the 0-2 MG group (100% vs. 33.4%, respectively, OR=35.9, 95%CI: 1.7-770, p=0.005). At the same time, positivity for the MTHFR 677T allele was not different between women from 0-2 MG and 3-5 MG groups (33.4% vs. 46.7%, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7).The simultaneous presence of the MTHFR 677T allele and MTRR 66GG genotype was more often detected in the 0-2 MG group than in the 3-5 MG group (33.3% vs. 10.0%, OR=4.5, 95%CI: 1.0-20.1, p=0.07).
Conclusion
We conclude that polymorphism of the FMM related genes could have an important role in mechanism of epigenetic disturbances in MDS associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): Genetic polymorphism, MDS, Methylation
Abstract: PB1905
Type: Publication Only
Background
Abnormal DNA methylation is often seen in patients with myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation process and, therefore, modify the risk of MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in MDS patients.
Methods
Fifty-one patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Twenty-one patients (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG) and 30 patients (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG).The MTRR 66 GG genotype was more frequently seen in the group 0-2 MG than in the group 3-5 MG (47.6% vs 13.3%, respectively, OR=5.9, 95%CI: 1.5-22.9, p=0.011). The MTHFR 1298 CC variant was present in 6 patients from the 3-5 MG and in 1 patient from the group 0-2 MG and (20.8% vs 4.8%, respectively, OR=5.0, 95%CI: 0.6-45.1, p=0.2).The presence of the MTHFR 677T allele was increased in male patients from the group 0-2 MG when compared to male patients in the 3-5 MG group (100% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01), and female patients from the 0-2 MG group (100% vs. 33.4%, respectively, OR=35.9, 95%CI: 1.7-770, p=0.005). At the same time, positivity for the MTHFR 677T allele was not different between women from 0-2 MG and 3-5 MG groups (33.4% vs. 46.7%, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7).The simultaneous presence of the MTHFR 677T allele and MTRR 66GG genotype was more often detected in the 0-2 MG group than in the 3-5 MG group (33.3% vs. 10.0%, OR=4.5, 95%CI: 1.0-20.1, p=0.07).
Conclusion
We conclude that polymorphism of the FMM related genes could have an important role in mechanism of epigenetic disturbances in MDS associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): Genetic polymorphism, MDS, Methylation
Type: Publication Only
Background
Abnormal DNA methylation is often seen in patients with myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation process and, therefore, modify the risk of MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in MDS patients.
Methods
Fifty-one patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Twenty-one patients (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG) and 30 patients (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG).The MTRR 66 GG genotype was more frequently seen in the group 0-2 MG than in the group 3-5 MG (47.6% vs 13.3%, respectively, OR=5.9, 95%CI: 1.5-22.9, p=0.011). The MTHFR 1298 CC variant was present in 6 patients from the 3-5 MG and in 1 patient from the group 0-2 MG and (20.8% vs 4.8%, respectively, OR=5.0, 95%CI: 0.6-45.1, p=0.2).The presence of the MTHFR 677T allele was increased in male patients from the group 0-2 MG when compared to male patients in the 3-5 MG group (100% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01), and female patients from the 0-2 MG group (100% vs. 33.4%, respectively, OR=35.9, 95%CI: 1.7-770, p=0.005). At the same time, positivity for the MTHFR 677T allele was not different between women from 0-2 MG and 3-5 MG groups (33.4% vs. 46.7%, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7).The simultaneous presence of the MTHFR 677T allele and MTRR 66GG genotype was more often detected in the 0-2 MG group than in the 3-5 MG group (33.3% vs. 10.0%, OR=4.5, 95%CI: 1.0-20.1, p=0.07).
Conclusion
We conclude that polymorphism of the FMM related genes could have an important role in mechanism of epigenetic disturbances in MDS associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): Genetic polymorphism, MDS, Methylation
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